Candidiasis caused by Candida albicans is probably the most common fungal infection of man. The organism probably utilizes at least three receptor/ligand systems in adhering to host cells. One of these receptors is a complement receptor (CR3) which recognizes the C3bi ligand and other ligands of endothelial cells containing a common arginine - glycine - aspartic acid (RGD) sequence. In addition, a CR2-like protein is also found in C. albicans which recognizes a C3d ligand. At this time it is uncertain whether Candida has a single protein with both activities or different proteins, each with different activities as is observed in mammalian cells. Preliminary evidence would indicate the former situation. This application has two specific aims. First, we will establish if the CR2 and CR3 activities are associated with a single protein or different proteins. We will sequence the CR2 gene and determine its structure. From its DNA sequence, an amino acid sequence will be deduced and assignments made about transmembrane, phosphorylation sites and extra and intracellular domains. The second specific aim will focus upon the function of the CR2 and CR3. Using both Cr2(-) and CR3(-) mutants we have isolated, we propose to transform these strains using cloned CR2 and CR3 genes and determine the effect of this transformation on adherence, virulence and interactions with phagocytic cells. There is strong evidence that CR3 function is associated with adherence and virulence. As an alternative, gene disruption can be used to convert CR3(+) and CR2(+) strains to a non-expressing phenotype. The interaction of the gene-disrupted strains with host cells can then be studied. This proposal, thus, will focus upon the interaction of specific cell surface components of Candida and its host and should provide answers in regard to the early stages of disease development.